The discovery of free floating fetal DNA (sometimes termed “cell free DNA” or “cfDNA”) in maternal blood allows the possibility of detecting chromosomal abnormality, aneuploidy, and aberration from blood samples. Fractional abundance of fetal DNA in maternal blood plasma is not constant and varies with a variety of factors including sample handling and gestational age.
When using DNA sequencing to identify chromosomal aberrations or genetic defects it is important to know the relative abundance of fetal DNA in the total population of DNA. For example, when fetal fraction is known, the statistical power (the probability of identifying anomalous cases, or the sensitivity) can be calculated by permutation methods or via integration of linear combinations or convolutions of non-central F distributions from alpha to infinity where alpha critical point for the significance (maximum likelihood of falsely calling an anomaly) of the population of scores under the null hypothesis of no aberration.
A drawback of existing methods for detecting fetal fraction is that they reply upon measures of the abundance of sex chromosomes (which can only be used to reliably measure relative abundance of male embryonic DNA) or mRNA sequence of genes known to be differentially expressed between pregnant and embryonic tissue (which is subject to variability of expression due to gestational age or other factors).
Estimation of fetal fraction can be difficult because of several nuisance factors including: parental ethnic differential population genetics parameters and sequencing errors. Therefore it is desirable to have methods robust in the presence of these and other commonly occurring confounding factors.